Sandbox 254

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Beta-2 Adrenergic Receptor
The Beta-2 Adrenergic Receptor (B2AR) is a G-protein coupled receptor (GPCR) which, when stimulated by a catecholamine, causes the relaxation of various smooth muscles, and the production of glucose by glycogenolysis and gluconeogenesis.

B2AR is a single chain that crosses the lipid membrane 7 times from the extracellular to cytoplasmic surface. 3 extracellular loops and 3 intracellular loops are formed as the 7 transmembrane helices (TM1 to TM7) pass back and forth through the membrane. The binding pocket is located to the center of the extracellular surface.

Conformational Changes Beta-2 Adrenergic Receptor
When an agonist is in the binding pocket a 2.1Å inward movement of TM5 at Ser207 is observed. This bulge at ser207 allows for a hydrogen bond between the ligand and the receptor. This interaction appears to be a key event in activation.

After the agonist binds, there is a rearrangement of interactions between residues located beneath the binding pocket that contributes to a rotation and outward movement of TM6 at Phe282. This change is associated with the breaking of the ionic lock between Glu268 in TM6 and Arg131 in TM3, resulting in an 11.4Å outward movement of the helix at the cytoplasmic face.

The coordinates for molecular morphs between inactive state of B2AR (2rh1) and active state (3p0g) were generated using iPyMOL and eMovie (http://www.weizmann.ac.il/ISPC/eMovie.html). Morphs, a series of 10 linear interpolations between a starting and finishing model, are useful when viewing the transition of a conformational change. This model of B2AR using morphs should not be thought of as precise animation of conformational changes upon activation but rather as a comparison of the inactive state to the active state.